Buspirone for Early Satiety and Symptoms of Gastroparesis

This is a multi-center, randomized, double-masked, placebo-controlled, parallel treatment
groups phase 2 trial to determine the effect of buspirone, a 5-hydroxytryptamine (5-HT) 1a
receptor agonist, on early satiety and postprandial fullness in participants with symptoms of
gastroparesis and with at least moderately severe symptoms of early satiety and/or
postprandial fullness. After enrollment, participants aged 18-75 years will be treated with
buspirone (10 mg three times per day) or a matching placebo for 4 weeks, followed by a 2-week
post-treatment washout period. The primary outcome for the study is 4-week change (week 4
minus baseline) in the 4-item postprandial fullness/early satiety subscore (higher scores
indicate worse symptoms) from the Patient Assessment of Gastrointestinal Disorders Symptom
Severity Index (PAGI-SYM) Gastroparesis Cardinal Symptom Index (GCSI). We hypothesize that
buspirone treatment will improve symptoms of postprandial fullness/early satiety compared to
treatment with placebo, as indicated by a lower (smaller, more negative) 4-week change in the
postprandial fullness/early satiety subscore in the buspirone arm compared to the placebo
arm; change for a participant will be calculated as subscore at 4-weeks minus subscore at
baseline.

Inclusion Criteria:

- Age 18 to 75 years of age at initial screening interview

- Symptoms compatible with gastroparesis or other functional gastric disorder for at
least 3 months (does not have to be contiguous) prior to initial screening interview

- Diagnosis of either diabetic or idiopathic gastroparesis

- Delayed or normal gastric emptying retention on screening 4-hour Gastric Emptying
Scintigraphy test

- Symptoms of gastroparesis measured by the 9-item PAGI-SYM Gastroparesis Cardinal
Symptom Index (GCSI) total score > 2.0 at enrollment

- Symptomatic with postprandial fullness/early satiety severity at enrollment using the
PAGI-SYM GCSI post-prandial fullness/early satiety subscore ≥ 3

- Upper endoscopy or upper GI series without ulcers or mass lesions in the 2 years prior
to enrollment

Exclusion Criteria:

- Post-surgical gastroparesis, including prior pyloromyotomy, pyloric resection,
vagotomy, bariatric surgery or post-Nissen fundoplication

- Another active disorder which could explain symptoms in the opinion of the
investigator

- Concurrent use of opiate narcotic analgesics more than 3 days per week

- Significant hepatic injury as defined by alanine aminotransferase (ALT) elevation of
greater than twice the Upper Limit of Normal (ULN) or a Child-Pugh score of 10 or
greater

- Significant renal impairment as defined by serum creatinine > 3.0

- Uncontrolled diabetes defined as HbA1c (%) of 10% or more within 60 days of enrollment

- Allergy to buspirone

- Concurrent or prior use (within 30 days) of monoamine oxidase (MAO) inhibitors

- Concurrent or prior use (within 30 days) of benzodiazepines

- Concurrent or prior use (within 30 days) of buspirone, warfarin, haloperidol, and
drugs to treat seizures (e.g., phenytoin and carbamazepine)

- Women breast feeding or known to be pregnant

- Any other condition, which in the opinion of the investigator would impede compliance
or hinder completion of the study

- Failure to give informed consent